The impact of COVID-19 monoclonal antibodies on clinical outcomes: A retrospective cohort study.

PURPOSE: Despite progress in the treatment of coronavirus disease 2019 (COVID-19), including the development of monoclonal antibodies (mAbs), more clinical data to support the use of mAbs in outpatients with COVID-19 is needed. This study is designed to determine the impact of bamlanivimab, bamlanivimab/etesevimab, or casirivimab/imdevimab on clinical outcomes within 30 days of COVID-19 diagnosis. METHODS: A retrospective cohort study was conducted at a single academic medical center with 3 campuses in Manhattan, Brooklyn, and Long Island, NY. Patients 12 years of age or older who tested positive for COVID-19 or were treated with a COVID-19-specific therapy, including COVID-19 mAb therapies, at the study site between November 24, 2020, and May 15, 2021, were included. The primary outcomes included rates of emergency department (ED) visit, inpatient admission, intensive care unit (ICU) admission, or death within 30 days from the date of COVID-19 diagnosis. RESULTS: A total of 1,344 mAb-treated patients were propensity matched to 1,344 patients with COVID-19 patients who were not treated with mAb therapy. Within 30 days of diagnosis, among the patients who received mAb therapy, 101 (7.5%) presented to the ED and 79 (5.9%) were admitted. Among the patients who did not receive mAb therapy, 165 (12.3%) presented to the ED and 156 (11.6%) were admitted (relative risk [RR], 0.61 [95% CI, 0.50-0.75] and 0.51 [95% CI, 0.40-0.64], respectively). Four mAb patients (0.3%) and 2.64 control patients (0.2%) were admitted to the ICU (RR, 01.51; 95% CI, 0.45-5.09). Six mAb-treated patients (0.4%) and 3.37 controls (0.3%) died and/or were admitted to hospice (RR, 1.61; 95% CI, 0.54-4.83). mAb therapy in ambulatory patients with COVID-19 decreases the risk of ED presentation and hospital admission within 30 days of diagnosis.

Bending the cost curve: time series analysis of a value transformation programme at an academic medical centre.

BACKGROUND: Reducing costs while increasing or maintaining quality is crucial to delivering high value care. OBJECTIVE: To assess the impact of a hospital value-based management programme on cost and quality. DESIGN: Time series analysis of non-psychiatric, non-rehabilitation, non-newborn patients discharged between 1 September 2011 and 31 December 2017 from a US urban, academic medical centre. INTERVENTION: NYU Langone Health instituted an institution-wide programme in April 2014 to increase value of healthcare, defined as health outcomes achieved per dollar spent. Key features included joint clinical and operational leadership; granular and transparent cost accounting; dedicated project support staff; information technology support; and a departmental shared savings programme. MEASUREMENTS: Change in variable direct costs; secondary outcomes included changes in length of stay, readmission and in-hospital mortality. RESULTS: The programme chartered 74 projects targeting opportunities in supply chain management (eg, surgical trays), operational efficiency (eg, discharge optimisation), care of outlier patients (eg, those at end of life) and resource utilisation (eg, blood management). The study cohort included 160 434 hospitalisations. Adjusted variable costs decreased 7.7% over the study period. Admissions with medical diagnosis related groups (DRG) declined an average 0.20% per month relative to baseline. Admissions with surgical DRGs had an early increase in costs of 2.7% followed by 0.37% decrease in costs per month. Mean expense per hospitalisation improved from 13% above median for teaching hospitals to 2% above median. Length of stay decreased by 0.25% per month relative to prior trends (95% CI -0.34 to 0.17): approximately half a day by the end of the study period. There were no significant changes in 30-day same-hospital readmission or in-hospital mortality. Estimated institutional savings after intervention costs were approximately $53.9 million. LIMITATIONS: Observational analysis. CONCLUSION: A systematic programme to increase healthcare value by lowering the cost of care without compromising quality is achievable and sustainable over several years.

The Swiss Cheese Conference: Integrating and Aligning Quality Improvement Education With Hospital Patient Safety Initiatives.

The Accreditation Council for Graduate Medical Education requires integration of quality improvement and patient safety education into graduate medical education (GME). The authors created a novel "Swiss Cheese Conference" to bridge the gap between GME and hospital patient safety initiatives. Residents investigate a specific patient safety event and lead a monthly multidisciplinary conference about the case. Resident presenters introduce the Swiss cheese model, present the case and their findings, and teach a patient safety topic. In groups, participants identify contributing factors and discuss how to prevent similar events. Presenters and stakeholders immediately huddle to identify next steps. The Swiss Cheese Conference has increased participants' comfort analyzing safety issues from a systems perspective, utilizing the electronic reporting system, and launching patient safety initiatives. The Swiss Cheese Conference is a successful multidisciplinary model that engages GME trainees by integrating resident-led, case-based quality improvement education with creation of patient safety initiatives.

Promoting High-Value Practice by Reducing Unnecessary Transfusions With a Patient Blood Management Program.

Although blood transfusion is a lifesaving therapy for some patients, transfusion has been named 1 of the top 5 overused procedures in US hospitals. As unnecessary transfusions only increase risk and cost without providing benefit, improving transfusion practice is an effective way of promoting high-value care. Most high-quality clinical trials supporting a restrictive transfusion strategy have been published in the past 5 to 10 years, so the value of a successful patient blood management program has only recently been recognized. We review the most recent transfusion practice guidelines and the evidence supporting these guidelines. We also discuss several medical societies' Choosing Wisely campaigns to reduce or eliminate overuse of transfusions. A blueprint is presented for developing a patient blood management program, which includes discussion of specific methods for optimizing transfusion practice.

Reducing liberal red blood cell transfusions at an academic medical center.

BACKGROUND: Educational and computerized interventions have been shown to reduce red blood cell (RBC) transfusion rates, yet controversy remains surrounding the optimal strategy needed to achieve sustained reductions in liberal transfusions. STUDY DESIGN AND METHODS: The purpose of this study was to assess the impact of clinician decision support (CDS) along with targeted education on liberal RBC utilization to four high-utilizing service lines compared with no education to control service lines across an academic medical center. Clinical data along with associated hemoglobin levels at the time of all transfusion orders between April 2014 and December 2015 were obtained via retrospective chart review. The primary outcome was the change in the rate of liberal RBC transfusion orders (defined as any RBC transfusion when the hemoglobin level is >7.0 g/dL). Secondary outcomes included the annual projected reduction in the number of transfusions and the associated decrease in cost due to these changes as well as length of stay (LOS) and death index. These measures were compared between the 12 months prior to the initiative and the 9-month postintervention period. RESULTS: Liberal RBC utilization decreased from 13.4 to 10.0 units per 100 patient discharges (p = 0.002) across the institution, resulting in a projected 12-month savings of $720,360. The mean LOS and the death index did not differ significantly in the postintervention period. CONCLUSION: Targeted education combined with the incorporation of CDS at the time of order entry resulted in significant reductions in the incidence of liberal RBC utilization without adversely impacting inpatient care, whereas control service lines exposed only to CDS had no change in transfusion habits.

The PrOSTE: identifying key components of effective procedural teaching.

RATIONALE: Novel approaches for faculty development and assessment of procedural teaching skills are needed to improve the procedural education of trainees. The Objective Structured Teaching Exercise (OSTE) entails a simulated encounter in which faculty are observed teaching a standardized student and has been used to evaluate teaching skills. Use of an OSTE to assess the teaching of central venous catheterization has not been reported. OBJECTIVES: The purpose of this study was to develop a procedural OSTE for subclavian central venous catheter (CVC) insertion and to determine specific aspects of procedural teaching associated with improved skills in novices. METHODS: Critical care faculty/fellows taught a standardized student to insert a CVC in a simulator. We assessed the instructor's teaching skills using rating scales to generate a procedural teaching score. After this encounter, the instructor taught novice medical students to place CVCs in simulators. Novices then independently placed catheters in simulators and were evaluated by trained observers using a checklist. Generalized estimating equations were used to examine the correlation between specific teaching behaviors and the novices' skills in CVC placement. MEASUREMENTS AND MAIN RESULTS: We recruited 10 participants to serve as teachers and 30 preclinical medical students to serve as novice learners. The overall mean procedural teaching score was 85.5 (±15.4). Improved student performance was directly related to the degree to which the teacher "provided positive feedback" (ß = 1.53, SE = 0.44, P = 0.001), "offered learner suggestions for improvement" (ß = 1.40, SE = 0.35, P < 0.001), and "demonstrated the procedure in a step-by-step manner" (ß = 2.50, SE = 0.45, P < 0.001). There was no significant correlation between total scores and student skills (ß = 0.06, SE = 0.46, P = 0.18). CONCLUSIONS: The OSTE is a standardized method to assess procedural teaching skills. Our findings suggest that specific aspects of procedural teaching should be emphasized to ensure effective transfer of psychomotor skills to trainees.

Treatment of Leptomeningeal Carcinomatosis in a Patient With Metastatic Cholangiocarcinoma.

A 49-year-old woman with cholangiocarcinoma metastatic to the lungs presented with new-onset unrelenting headaches. A lumbar puncture revealed malignant cells consistent with leptomeningeal metastasis from her cholangiocarcinoma. Magnetic resonance imaging (MRI) of the brain revealed leptomeningeal enhancement. An intrathecal (IT) catheter was placed and IT chemotherapy was initiated with methotrexate. Her case is notable for the rarity of cholangiocarcinoma spread to the leptomeninges, the use of IT chemotherapy with cytologic and potentially symptomatic response, and a possible survival benefit in comparison to previously reported cases of leptomeningeal carcinomatosis secondary to cholangiocarcinoma.

Phosphatase-resistant gap junctions inhibit pathological remodeling and prevent arrhythmias.

RATIONALE: Posttranslational phosphorylation of connexin43 (Cx43) has been proposed as a key regulatory event in normal cardiac gap junction expression and pathological gap junction remodeling. Nonetheless, the role of Cx43 phosphorylation in the context of the intact organism is poorly understood. OBJECTIVE: To establish whether specific Cx43 phosphorylation events influence gap junction expression and pathological remodeling. METHODS AND RESULTS: We generated Cx43 germline knock-in mice in which serines 325/328/330 were replaced with phosphomimetic glutamic acids (S3E) or nonphosphorylatable alanines (S3A). The S3E mice were resistant to acute and chronic pathological gap junction remodeling and displayed diminished susceptibility to the induction of ventricular arrhythmias. Conversely, the S3A mice showed deleterious effects on cardiac gap junction formation and function, developed electric remodeling, and were highly susceptible to inducible arrhythmias. CONCLUSIONS: These data demonstrate a mechanistic link between posttranslational phosphorylation of Cx43 and gap junction formation, remodeling, and arrhythmic susceptibility.

Gap junction remodeling and spironolactone-dependent reverse remodeling in the hypertrophied heart.

Pressure overload is a common pathological insult to the heart and the resulting hypertrophy is an independent risk factor for sudden cardiac death. Gap junction remodeling (GJR) has been described in hypertrophied hearts; however, a detailed understanding of the remodeling process and its effects on impulse propagation is lacking. Moreover, there has been little progress developing therapeutic strategies to diminish GJR. Accordingly, transverse aortic banding (TAC) was performed in mice to determine the effects of progressive pathological hypertrophy on connexin (Cx)43 expression, posttranslational phosphorylation, gap junction assembly, and impulse propagation. Within 2 weeks after TAC, total and phospho-Cx43 abundance was reduced and incorporation of Cx43 into gap junctional plaques was markedly diminished. These molecular changes were associated with progressive slowing of impulse propagation, as determined by optical mapping with voltage-sensitive dyes. Treatment with the aldosterone receptor antagonist spironolactone, which has been shown to diminish sudden arrhythmic death in clinical trials, was examined for its effects on GJR. We found that spironolactone blunted the development of GJR and also potently reversed established GJR, both at the molecular and functional levels, without diminishing the extent of hypertrophy. These data suggest a potential mechanism for some of the salutary electrophysiological and clinical effects of mineralocorticoid antagonists in myopathic hearts.